Peripheral nerve fevers of adult rats can regenerate into silicone tubes wherein they reform a new nerve segment. We used an electron microscopical histochemical technique to determine whether barrier function to macromolecules developed in the blood vessels and perineurial-like cells that appeared. Nerve segments permanently enclosed in or free of tubes for three months were examined with the barrier tracer horseradish peroxidase (HRP). All segments contained remyelinated axons, blood vessels and perineurial-cells which divided the nerve into mini-compartments. Most vessels were excluded from the endoneurium of the mini-compartments, and intravenously injected HRP, which was retained by vessels in normal nerves, leaked out of them. The regenerated endothelial cells stained for alkaline phosphatase activity equivalent to that seen in HRP impermeable vessels of normal nerve. The perineurial barrier was analyzed in segments soaked in HRP in situ. HRP entered only the superficial fascicle of segments formed in permanent tubes because a dense layer of collagen developed between the nerve and inner tube lining. The collagen layer was absent after early tube removal, and HRP penetrated the deeper perineurial-like sheaths and entered the endoneurium where it spread around the nerve fibers. These results demonstrated that neither blood nor perineurial permeability barriers exist in nerves reconstructed in tubes. We have continued to investigate the immunological factors that determine allograft immunogenicity. Ganglia grafts were transplanted between congenic B10 mice that differ only in Class 1 (K region) or Class 2 (region) histocompatibility antigens. Frozen sections revealed that the grafts were rejected. The lack of an 1 region stimulus does not lead to allograft tolerance since K region disparities alone can elicit rejection.